Download Giant idiopathic pyoderma gangrenosum

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts
no text concepts found
Transcript
Our Dermatology Online
Case Report
Giant idiopathic pyoderma gangrenosum at an
unusual site with highly elevated c-ANCA levels: A
rare association
Lovleen Kaur, Mohita Mahajan, Parul Chojer, Bharat Bhushan Mahajan,
Suresh Kumar Malhotra
Department of Dermatology, Venereology and Leprosy, Government Medical College, Amritsar, India
Corresponding author: Dr. Lovleen Kaur, E-mail: [email protected]
ABSTRACT
Pyoderma gangrenosum (PG) is a rare neutrophilic disorder with an incidence rate of 3–10 cases per million per year,
characterized by classically painful and aseptic ulcers, which may be associated with underlying systemic diseases. The
pathergy reaction is seen in one-fourth of patients with PG. Accurate and timely diagnosis is crucial, as PG is known
for its rapid progression. The management of PG is challenging and depends on its severity and rate of progression.
An underlying systemic involvement should be sought even in spite of no symptoms. Herein, we report a case of giant
pyoderma gangrenosum involving almost the entire left buttock with exceptionally raised c-ANCA levels, but no underlying
systemic abnormality. The patient reported intense pain, rapid progression of the ulcers, an inability to perform daily
activities, was significantly morbid and pathergy-positive. Aggressive and early management is required in cases such as
this. A dramatic response was achieved with a combination of cyclosporine, dapsone, and methylprednisolone pulses.
Key words: Pyoderma gangrenosum; Neutrophilic dermatoses; ANCA; Pathergy
INTRODUCTION
Pyoderma gangrenosum (PG) is a rare neutrophilic
dermatosis characterized by noninfectious ulcers, usually
involving the lower extremities, with an estimated
incidence rate of 3–10 cases per million per year [1].
PG is associated with underlying systemic diseases
in around 50% of cases [2]. Modified immunological
response and altered neutrophilic chemotaxis have been
proposed as the underlying mechanism of pathogenesis.
Pathergy is seen in one-fourth of cases of PG [3]. Herein,
we report a case of giant pyoderma gangrenosum on an
atypical site—the left buttock—with highly elevated
c-ANCA levels, treated with multidrug therapy.
CASE REPORT
A 28-year-old female presented herself to our
dermatology outpatient department with a history of
recurrent progressive ulcerations involving the lower
extremities and left buttock. The ulcerations had
shown two years prior as a single nodular abscess over
the right ankle, which had been incised and drained
by a surgeon. Pathergy developed at the incision site to
form a painful nonhealing ulcer. As the ulcer expanded,
the patient noted simultaneous development of new
ulcers bilaterally on the shins, ankles, and the dorsum of
both feet within several days. While some of the ulcers
healed with scarring, others progressively enlarged
despite continuous treatment with oral steroids,
doxycycline, and azathioprine elsewhere. Intermittent
remissions and relapses of the lesions occurred during
these two years.
Later, the patient developed three small ulcers on the
left buttock while on treatment with azathioprine, oral
steroids, and minocycline for two consecutive months.
The edge of one ulcer was biopsied, after which the ulcers
How to cite this article: Kaur L, Mahajan M, Chojer P, Mahajan BB, Malhotra SK. Giant idiopathic pyoderma gangrenosum at an unusual site with highly
elevated c-ANCA levels: A rare association. Our Dermatol Online. 2021;12(1):58-61.
Submission: 13.05.2020;
Acceptance: 01.08.2020
DOI: 10.7241/ourd.20211.15
© Our Dermatol Online 1.2021
58
www.odermatol.com
enlarged and coalesced to form a large necrotic ulcer
within a period of three days, thus, again, demonstrating
the presence of a pathergy reaction. No further medical
or surgical history of significance was recorded.
An examination revealed a giant oval ulcer 23 ×
17 cm in size covered with a necrotic brown crust
on the left buttock (Figs. 1a and 1b). Manipulation
produced purulent exudate and oozing of the blood.
Another deep-seated ulcer, 2 × 3 cm in size and
adjacent to the initial, was present medially. Its base
was not fixed to the underlying structures. Multiple
discrete erythematous-to-violaceous warm and tender
nodules—several with central suppuration—were
present over both lower limbs, predominantly over the
thighs, indicating primary lesions. A single left inguinal
lymph node 2 × 2 cm in size was present. Multiple
healed atrophic cribriform scars were evident on both
the shins and the dorsum of the feet (Figs. 2a and 2b).
A systemic examination was unremarkable.
Routine and specific investigations revealed hemoglobin
at 6.6 g/dL, a total leukocyte count of 13,000 with
neutrophilia (90%), ESR at 102, C-reactive protein
at 49.4, and rheumatoid factor at 298.7. c-ANCA
(antineutrophil cytoplasmic antibody) levels were as
high as 76.0 units/mL. ANA (antinuclear antibody),
anti-CCP (anti-cyclic citrullinated peptide), p-ASCA
(anti-saccharomyces cerevisiae antibody), and p-ANCA
(perinuclear-staining ANCA) were normal. Fecal occult
blood was absent. Colonoscopy was inconclusive of
inflammatory bowel disease (IBD), showing several tiny
ileal ulcerations with the rest of the intestinal mucosa
completely normal. A pus culture revealed growth of
Escherichia coli. Tubercular and fungal cultures revealed
no growth. A deep skin biopsy from the edge of the ulcer
revealed partially treated vasculitis, endothelial swelling,
intravascular thrombi, and large neutrophilic aggregates
in the subcutaneous tissue, consistent with the diagnosis
of PG (Figs. 3a and 3b). No grains or AFB were seen.
The patient was given a blood transfusion and
IV antibiotics. Once the secondary infection was
controlled, methylprednisolone pulses for five days,
oral cyclosporine 200 mg/day, and dapsone 100 mg/day
were initiated. Anticipating the risk of pathergy, surgical
debridement was discouraged. Desloughing with
hydrogen peroxide and daily sterile dressings were
performed. Within two weeks of initiating treatment,
the purulent exudate reduced markedly and the ulcer
began re-epithelizing with healthy granulation tissue
at the floor (Fig. 4). Complete healing was observed
© Our Dermatol Online 1.2021
a
b
Figure 1: (a) The initial presentation as a giant necrotic crusted lesion
covering almost the entire left buttock (day 1). (b) The ulcer covered
with frank purulent exudate after desloughing (day 3).
a
b
Figure 2: (a) Atrophic cribriform-like scarring on the lateral aspect of
the right foot and the right lower leg. (b) The dorsum of the left foot
and the medial aspect of the left ankle.
a
b
Figure 3: (a) A photomicrograph of the edge of the ulcer (gross view)
(H&E, scanner view). (b) Intravascular thrombi and large neutrophilic
aggregates in the subcutaneous tissue (H&E, 10×).
in two months, although the atrophic hyperpigmented
scar was still present (Fig. 5). The patient was, however,
fully satisfied. Drugs were gradually tapered and
stopped after six months. Currently, the patient is off
cyclosporine and dapsone, and has had no recurrence
after nine months of continuous follow-ups. The
levels of ESR, CRP, and c-ANCA (4.0 units/mL) have
returned to normal.
DISCUSSION
Pyoderma gangrenosum ulcers are classically painful
and aseptic, although superinfection may eventually
59
www.odermatol.com
presentations in the form of PG-like lesions have been
reported in 10% of cases of WG [4]. Although c-ANCA
levels were severely raised, no manifestation suggestive
of upper and lower airway and renal involvement
were found in this case to fulfil the classical triad of
Wegener’s granulomatosis (WG).
Figure 4: A response two weeks after therapy, with epithelization
evident in the center and healthy granulation tissue at the floor of the
ulcer.
Figure 5: The nearly complete resolution of the ulcer after two months
of therapy.
occur, probably, as in our case, because of an odd
anatomical site. This ulcer, on removal of the necrotic
crust, showed a purulent base with undermined
asymmetrical borders. Extension of the lesion on
surgical incision was observed twice, indicating a
pathergy reaction. Multiple old healed cribriform
scars again favored the diagnosis of PG. Systemic
associations of ulcerative colitis, Crohn’s disease,
rheumatoid arthritis, hematological malignancies, and
monoclonal gammopathy have been reported [2].
Skin manifestations in both classical and localized
Wegener’s granulomatosis (WG) have been reported in
around 50% of cases [4]. They may present themselves
as papulonecrotic, urticarial, vesicular lesions, palpable
purpura or necrotizing ulcers resembling pyoderma
gangrenosum [5]. It must be noted that initial
© Our Dermatol Online 1.2021
Other than the former, ANCA-associated vasculitis
(AAV) has been reported with neutrophilic dermatoses
(ND). Indeed, several clinical conditions, such as
inflammatory bowel diseases (IBDs), can exhibit both
ND and ANCA, especially their anti-MPO subtypes [6].
However, the specific targets of these antibodies, as of
now, have not been identified. One study suggests that,
in cases of neutrophilic dermatosis, the patient may
be tested for ANCA and, if positive, careful attention
should be paid to observe signs suggestive of systemic
vasculitis [7]. Another study, conducted by Kawakami
et al., proves the pathologic role of ANCA beyond
vasculitis and suggests that c-ANCA may be directly
or indirectly pathogenic in PG and/or may be produced
because of neutrophilic activation and apoptosis in
cases with PG, resulting in a self-amplifying loop [8].
Our patient displayed highly elevated c-ANCA levels,
but no sign of WG or IBD was discovered.
Therapy in cases with PG is a matter of debate, as
there is no uniformly effective treatment. The aim is
to treat the underlying cause. In a rapidly progressive
disease with significant morbidity, an aggressive
treatment approach to halt the immunological process
is crucial. Hence, methylprednisolone pulses, followed
by cyclosporine, for its quick onset of action, and
dapsone, for its antineutrophilic and steroid-sparing
effects are preferred in rapidly progressing cases such
as ours, in which such a regimen dramatically improved
the outcome and expedited recovery in two months
with sustained remission. However, regular follow-ups
are necessary to detect signs of recurrence; otherwise,
rare cases may display this as an early manifestation of
Wegener’s granulomatosis or ulcerative colitis.
CONCLUSION
Pyoderma gangrenosum, a type of neutrophilic
dermatosis, oftentimes causes significant agony to
the patient. PG is typically noninfectious, painful,
and rapidly progressive, and so demands aggressive
management with immunosuppressants, as in our case.
Surgical maneuvers should be discouraged because
of the high risk of pathergy. Common sites are the
60
www.odermatol.com
lower limbs, but PG may present itself at any site,
making diagnosis problematic. A thorough systemic
examination and a battery of investigations should
be performed in search for an underlying systemic
abnormality. c-ANCA, although considered highly
specific to Wegener’s granulomatosis, may also be a
possible marker for ulcerative colitis or AAV associated
with PG; hence, long-term follow-ups are obligatory
because pyoderma gangrenosum may be an initial
presentation of either of these underlying disorders.
2.
3.
4.
5.
6.
Consent
The examination of the patient was conducted according to the
principles of the Declaration of Helsinki.
The authors certify that they have obtained all appropriate patient
consent forms, in which the patients gave their consent for images
and other clinical information to be included in the journal. The
patients understand that their names and initials will not be
published and due effort will be made to conceal their identity,
but that anonymity cannot be guaranteed.
REFERENCES
1.
Cozzani E, Gasparini G, Parodi A. Pyoderma gangrenosum: a
systematic review. G Ital Dermatol Venereol. 2014;149:587-600.
© Our Dermatol Online 1.2021
7.
8.
Rodríguez-Zúñiga MJM, Heath MS, Gontijo JRV, Ortega-Loayza AG.
Pyoderma gangrenosum: a review with special emphasis on Latin
America literature. An Bras Dermatol. 2019;94:729-43.
Ahronowitz I, Harp J, Shinkai K. Etiology and management of
pyoderma gangrenosum: a comprehensive review. Am J Clin
Dermatol. 2012;13:191-211.
Nasir N, Ali SA, Mehmood Riaz HM. Cutaneous ulcers as initial
presentation of localized granulomatosis with polyangiitis: a
case report and review of the literature. Case Rep Rheumatol.
2015;2015:517025.
Chhabra S, Minz RW, Rani L, Sharma N, Sakhuja V, Sharma A.
Immune deposits in cutaneous lesions of Wegener’s granulomatosis:
predictor of an active disease. Indian J Dermatol. 2011;56:758-62.
Elkadri AA, Stempak JM, Walters TD, Lal S, Griffiths AM,
Steinhart AH, et al. Ser um antibodies associated with
complex inflammatory bowel disease. Inflammat Bowel Dis.
2013;19:1499-505.
de Boysson H, Silva NM, de Moreuil C, Néel A, de Menthon M,
Meyer O, et al. Neutrophilic dermatoses in antineutrophil
cytoplasmic antibody-associated vasculitis: a French multicenter
study of 17 cases and literature review. Medicine. 2016;95:e2957.
Kawakami T, Kawanabe T, Saito C, Kannari M, Mizoguchi M,
Nagafuchi H, et al. Clinical and histopathologic features of
8 patients with microscopic polyangiitis including two with
a slowly progressive clinical course. J Am Acad Dermatol.
2007;57:840-8.
Copyright by Kaur Lovleen, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium,
provided the original author and source are credited.
Source of Support: Nil, Conflict of Interest: None declared.
61